Aldehydes are chemically reactive substances having toxic effects in people and animals. Aldehydes are catalyzed into less reactive carboxylic acids via aldehyde dehydrogenase (ALDH), which are excreted from the body as such or as conjugates (Lindahl, Crit. Rev. Biochem. Mol. Biol. 1992, 27, 283-335). Multiple forms of ALDH exist including, for instance, cytosolic ALDH1A1 and mitochondrial ALDH1B1 and ALDH2, that catalyze a wide spectrum of aldehydes (Yoshida et al., Eur. J. Biochem. 1998, 251, 549-557; Vasiliou et al., Pharmacogenetics 1998; 9, 421-434).
Owing to its high affinity (Km<5 μM) for acetaldehyde, ALDH2 is prominent among the dehydrogenases for the removal of acetaldehyde, which is, for example, the major aldehyde product of ethyl alcohol catabolism in people (Klyosov, Biochemistry 1996, 35, 4457-4467; Kurys et al., J. Biol. Chem. 1989, 264, 4715-4721). Acetaldehyde is linked to acute symptoms such as flushing, tachycardia, shortness of breath, dizziness, nausea, vomiting and headache as well as to long-term effects like increased risk of cancers of the upper digestive tract, breast cancer, liver disease, Alzheimer's disease, hypertension and myocardial infarction (see Visapaa et al., Gut 2004, 53, 871-876; Yokoyama et al., Jpn. J. Clin. Oncol. 2003, 33(3), 111-121; Ohsawa et al., J. Hum. Genet. 2003, 48, 404-409; and references cited therein). People with a variant ALDH2 (termed ALDH2*2 herein) having reduced activity on acetaldehyde catalysis exhibit alcohol-related sensitivity, e.g., facial flushing, tachycardia, etc., when drinking small portions of ethyl alcohol that would not normally elicit such reactions in carriers of the more prevalent ALDH2 isoform (Goedde et al., Hum. Genet. 1992, 88, 344-346; Xiao et al., J. Clin. Invest. 1995, 96, 2180-2186).
Exposure of the human population, particularly those in certain occupations, to acetaldehyde can be significant. For example, acetaldehyde is found in tobacco smoke and in automobile and diesel exhaust. It is also used or is generated in the manufacture of, for example, synthetic flavorings for processed foods, fumigants, and room air deodorizers. Combustion of wood, some plastics and some hard and soft polyurethane foams produce acetaldehyde (Allyl Compounds, Aldehydes, Epoxides, and Peroxides. IARC Monographs on the Evaluation of Carcinogenic Risk of Chemicals to Humans, vol. 36. Lyon, France: International Agency for Research on Cancer, 369 pp.).
Compositions and methods useful for assisting in maintaining low aldehyde levels in vivo would be advantageous for avoiding the undesirable and harmful effects of aldehydes, such as acetaldehyde.
Ginseng extracts are reported to have useful properties for treating cancer, enhancing the elimination of alcohol from blood, modulating alcohol dehydrogenase and ALDH activities, inter alia (see, e.g., Helms, Alternative Medicine Review 2004, 9(3), 259-274; Lee et al., Clinical and Experimental Pharmacology & Physiology 1987 14, 543-546; Joo et al., Korean Biochem. J. 1977, 10(2), 109-120). However, the active principals of the different ginseng plant species can include many different saponins, polysaccharides, flavonoids and volatile oils. For instance, over forty different ginseng saponins, termed ginsenosides, have been identified which are classified into various types including the protopanaxadiol (PPD), protopanaxatriol (PPT) and oleanonic acid types (see, e.g., Zhu et al., Chem. Pham. Bull. 2004, 52, 995-998 and Yu et al., Chem. Pharm. Bull. 2007, 55(2), 231-235, each of which is incorporated herein by reference in its entirety). Moreover, ginseng extracts vary considerably in their composition of active principals depending on various parameters such as age or type of root used and extraction method applied (see, e.g., U.S. Pat. No. 4,157,894).